Pathologic Characteristics of Cancers Detected in the Prostate Cancer Prevention Trial: Implications for Prostate Cancer Detection and Chemoprevention

Abstract

The Prostate Cancer Prevention Trial (PCPT) showed a risk of prostate cancer at prostatespecific antigen (PSA) <4.0 ng/mL and that prostate cancer risk is reduced by finasteride. A major concern about early detection by PSA and prevention by finasteride is that they may involve biologically inconsequential tumors. We reviewed the pathologic characteristics of prostate biopsies from men in the placebo and finasteride groups of the PCPT. We examined tumor pathology characteristics stratified by level of PSA for men in the placebo group who underwent radical prostatectomy. Seventy-five percent of all cancers and 62% of Gleason score ≤6 cancers in the PCPT met the biopsy criteria for clinically significant tumors. Surrogate measures for tumor volume (number of cores positive, percent cores positive, linear extent, and bilaterality) and risk of perineural invasion were lower in men who received finasteride. The PSA-associated risks of insignificant cancer were 51.7% (PSA, 0-1.0 ng/mL), 33.7% (1.1-2.5 ng/mL), 17.8% (2.6-4.0 ng/mL), and 11.7% (4.1-10 ng/mL). Conversely, the risks of high-grade (Gleason score ≥7) tumors for the same PSA strata were 15.6%, 37.9%, 49.1%, and 52.4%, respectively. These data highlight the dilemma of PSA when used for screening: Lower cutoff levels increase detection of insignificant disease, but cure is more likely, whereas higher cutoff levels make detection of significant cancer more likely, but cure is less likely. Therefore, the effectiveness of finasteride in preventing prostate cancer, including Gleason score ≤6 cancer, with meaningful rates of significant disease in the PCPT suggests that cutoff values for PSA screening should be individualized and that men undergoing screening should be informed of the opportunity to reduce their risk of disease with finasteride.

First-year costs of treating prostate cancer: estimates from SEER-Medicare data

“…1 Although initially the development of high-grade PCa under finasteride treatment was viewed as a detrimental effect, 1 recently published new analyses demonstrated this to be an artifact, and in fact, these analyses suggest overall a 30% reduction in the period prevalence of PCa under finasteride with no increased risk for high-grade cancer. [2][3][4][5] Dutasteride 6 is also currently being evaluated in phase III placebo-controlled trials. As additional clinical data become available regarding the benefits and risks of these pharmacologic agents, an examination of their economic impact will also be important.…”

Cancer Prevention Research: Back to the Future

“…New PCPT analyses reported in CaPR, however, have renewed hope for hormonal prostate cancer prevention with finasteride. These analyses found that finasteride prevented clinically meaningful disease and did not increase aggressive disease (87)(88)(89)(90), possibly eventually eliminating the related obstacles to finasteride acceptance (86). The case for this agent class has been further strengthened by very recently reported results of a trial of another 5α-reductase inhibitor, dutasteride.…”

Circulating microRNAs: macro-utility as markers of prostate cancer?

“…Indeed, !50% of men who have undergone a biopsy in response to a PSA reading of O4.0 ng/ml are diagnosed with PCa (Grubb et al 2008, Schroder et al 2009). Secondly, w15% of men with a 'negative' PSA reading (0-4 ng/ml) have PCa (Thompson et al 2004, Lucia et al 2008. Finally, and most importantly, large randomized trials in the USA and Europe have demonstrated that PSA screening contributes heavily to the overdiagnosis and overtreatment of PCa (Andriole et al 2009, Schroder et al 2009).…”